In recent years, along with rapidly aging population, an increase in dementia diseases including Alzheimer's disease (AD) as a typical example has become a serious social problem. At present, methods of clinically diagnosing AD include Hasegawa style, ADAS, and MMSE. In all of these methods, a method of quantitatively evaluating a decrease in the cognitive function of an individual, who is suspected of having AD, is generally used. Other than these methods, image diagnostic techniques (MRI, CT, etc.) are subsidiarily used. However, these diagnostic methods are insufficient for the definitive diagnosis of AD. For such definitive diagnosis, it is necessary to confirm the appearance of senile plaque and neurofibril in a brain biopsy performed in life, or in a pathological histological examination performed on the brain after death. Accordingly, it is difficult for the current diagnostic methods to diagnose AD at an early stage before the occurrence of a wide range of brain disorder. To date, there have been several reports regarding biological diagnostic markers for AD. However, such diagnostic markers that are clinically practical have not yet been developed. Under such circumstances, there is a high social need for the early diagnosis of AD, and thus it is strongly desired that such a diagnostic method be rapidly developed.
Senile plaque is a cerebral lesion that is the most characteristic of AD, and the main constituent thereof is an amyloid β protein having a β sheet structure. It is considered that imaging of such senile plaque from outside the body results in the establishment of an effective diagnostic method for AD. However, for such imaging, a probe compound that is specifically binds to such an amyloid β protein is necessary. To date, several derivatives having congo red or thioflavine T as a base structure have been reported (Patent Documents 1 and 2, and Non-Patent Document 1). However, such compounds have been considerably problematic in terms of low binding specificity to an amyloid β protein, low permeability to a blood-brain barrier, slow clearance caused by non-specific bond in brain, and the like. Therefore, the reported compounds have not yet been practically used in the diagnosis of diseases that are associated with accumulation of amyloid under the present circumstances.
[Patent Document 1] Japanese Patent Application Laid-Open No. 2004-250407
[Patent Document 2] Japanese Patent Application Laid-Open No. 2004-250411
[Non-Patent Document 1] W. E. Klunk et al., Annals of Neurology, Vol. 55, No. 3, March 2004, 306-319